6520111Burnham Center for Chemical GenomicsSBCCG-A958-HIF-1a-DryPowder_Panel-Assay201421SAR Analysis small molecule inhibitors of HIF-1a in a panel assayData Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, La Jolla, CA)Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)Grant Number: 1 R03 DA033980-01A1Assay Provider: Mei Yee Koh, Ph.D., University of Texas M.D. Anderson Cancer CenterMost solid tumors and their metastases experience regions of hypoxia, which promotes both tumor progression and resistance to therapy. Critical mediators of the hypoxic response are the hypoxia-inducible factors HIF-1a and HIF-2a. HIF-1a and HIF-2a are non-redundant and regulate both overlapping and unique downstream target genes. HIF-1a has been associated with poor patient survival in multiple tumor types and is currently being pursued as a target for inhibition for cancer therapy(1,2). HIF-2a has also been associated with poor patient prognosis in specific tumor types such as renal cell carcinoma (RCC), neuroblastoma, glioblastoma (GBM) and non-small cell lung cancer (NSCLC)(3-6). The tumor type specific function of HIF-2a has been linked with the ability of HIF-2a (but not HIF-1a) to co-operate with a number of oncoproteins such as c-Myc, EGFR and K-Ras(5,7,8) and also to activate genes involved in proliferation, invasion and in the maintenance of cancer stem cells (CSCs)(9,10). Hence, although the validity of HIF-1a as a target in multiple tumor types cannot be denied, emerging data suggest that in certain settings, the specific inhibition of HIF-2a versus HIF-1a would be warranted. Additionally, the newly established role of HIF-2a in the maintenance of neoplastic but not in normal stem cells, suggests that HIF-2a inhibition may provide a novel strategy for the targeting of CSCs 11, 12, 13. Thus our hypothesis is that the specific inhibition of HIF-2a will be a useful strategy for treating HIF-2a driven tumors and for targeting the CSC population. The overall goal of the study is to identify small molecule specific inhibitors of HIF-2a that will lead to the development of new anti-cancer therapies. The goal of this assay is to confirm hits in "uHTS identification of HIF-2a Inhibitors in a luminesence assay", AID 624352. Compounds that are active in the Hif-2a and HIF-2a_PANC assays, but inactive in the HIF-1a counter screen are selective in the panel. Compounds are either acquired from commercial sources or synthesized internally.REFERENCES1. Gordan J D, Bertout J A, Hu C J, Diehl J A,Simon M C. HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 2007; 11: 335-47. 2. Scrideli C A, Carlotti C G, Jr., Mata J F, Neder L, Machado H R, Oba-Sinjo S M et al. Prognostic significance of co-overexpression of the EGFR/IGFBP-2/HIF-2A genes in astrocytomas. J Neurooncol 2007; 83: 233-9. 3. Kim W Y, Perera S, Zhou B, Carretero J, Yeh J J, Heathcote S A et al. HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J Clin Invest 2009; 119: 2160-70. 4. Holmquist-Mengelbier L, Fredlund E, Lofstedt T, Noguera R, Navarro S, Nilsson H et al. Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype. Cancer Cell 2006; 10: 413-23. 5. Franovic A, Holterman C E, Payette J,Lee S. Human cancers converge at the HIF-2alpha oncogenic axis. Proc Natl Acad Sci U S A 2009; 106: 21306-11. 6. Giatromanolaki A, Koukourakis M I, Sivridis E, Turley H, Talks K, Pezzella F et al. Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival. Br J Cancer 2001; 85: 881-90. 7. Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 2009; 15: 501-13. 8. Seidel S, Garvalov B K, Wirta V, von Stechow L, Schanzer A, Meletis K et al. A hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. Brain 2010; 133: 983-95. 9. Pietras A, Hansford L M, Johnsson A S, Bridges E, Sjolund J, Gisselsson D et al. HIF-2alpha maintains an undifferentiated state in neural crest-like human neuroblastoma tumor-initiating cells. Proc Natl Acad Sci U S A 2009; 106: 16805-10. 10. Qing G,Simon M C. Hypoxia inducible factor-2alpha: a critical mediator of aggressive tumor phenotypes. Curr Opin Genet Dev 2009; 19: 60-6. 11. Carroll V A,Ashcroft M. Role of hypoxia-inducible factor (HIF)-1alpha versus HIF-2alpha in the regulation of HIF target genes in response to hypoxia, insulin-like growth factor-I, or loss of von Hippel-Lindau function: implications for targeting the HIF pathway. Cancer Res 2006; 66: 6264-70. 12. Dutta D, Ray S, Vivian J L,Paul S. Activation of the VEGFR1 chromatin domain: an angiogenic signal-ETS1/HIF-2alpha regulatory axis. J Biol Chem 2008; 283: 25404-13. 13. Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S et al. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med 16: 678-86.HIF-1aAssay Materials:MIAPaCa-2 pancreatic cells (Assay Provider)DMEM 4.5 g/l glu w/glu w/o phenol red (CellGro 17-205-CV)Fetal Bovine Serum (Hyclone SH30396.03)Penicillin Streptomycin solution (Invitrogen 15140122)L-glutamine (100X ) (Invitrogen 25030081)G418 (50 mg/mL) (Omega Scientific GN-04)TrypLE (Invitrogen 12563)Desferoxiamine (Sigma D9533-1G)One-Glo (Promega E6120)I. Cell Addition1- Dispense 3 uL/well of cells at 2.5x10^5 cells/ml to col 1-48. 2- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.3 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.II. Reagent Addition4-Dispense 1 ul/well 200 uM desferoxiamine in assay media to columns 5-48III. Compound Addition:5- Transfer test compounds to columns 5-44 and DMSO to columns 1-4 and 45-48 using the Labcyte ECHO 555. Transfer volume of test compound is 40-2.5nl of 10 mM stock and 40-2.5 nl of 0.3125mM stock. All wells are backfilled to 40 nl DMSO (1% DMSO) 6- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.7 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.IV. Reagent Addition8- Dispense 3 uL/well of One-Glo using Combi dispenser to all columns.9- Spin down plates without lids on Vspin at 2000 rpm for 1 min10- Incubate plates at room temperature for 10 minsV. Reading plates:11-Read on luminescence protocol on EnvisionHIF-2a AssayAssay Materials:786-0 renal cell carcinoma cells (Assay Provider)DMEM 4.5 g/l glu w/glu w/o phenol red (CellGro 17-205-CV)Fetal Bovine Serum (Hyclone SH30396.03)Penicillin Streptomycin solution (Invitrogen 15140122)L-glutamine (100X ) (Invitrogen 25030081)G418 (50 mg/mL) (Omega Scientific GN-04)TrypLE (Invitrogen 12563)Steady-Glo (E2550)I. Compound Addition:1- Transfer test compounds to columns 5-44 and DMSO to columns 1-4 and 45-48 using the Labcyte ECHO 555. Transfer volume of test compound is 40-2.5 nl from 10 mM stock and 40-2.5 nl from 0.3125 mM stock. All wells are backfilled to 40 nl DMSO (1% DMSO) II. Reagent Addition2- Dispense 4 uL/well of assay media to col 1-4.3- Dispense 4 uL/well of cells at 2.5x10^5 cells/ml to col 5-48.4- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.5 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.6- Dispense 3 uL/well of Steady-Glo using Biotek dispenser to all columns.7- Spin down plates without lids on Vspin at 2000 rpm for 1 min8- Incubate plates at room temperature for 10 minsIII. Reading plates:9-Read on luminescence protocol on ViewluxHIF-2a PANCAssay Materials:PANC pancreatic cells (Assay Provider)DMEM 4.5 g/l glu w/glu w/o phenol red (CellGro 17-205-CV)Fetal Bovine Serum (Hyclone SH30396.03)Penicillin Streptomycin solution (Invitrogen 15140122)L-glutamine (100X ) (Invitrogen 25030081)G418 (50 mg/mL) (Omega Scientific GN-04)TrypLE (Invitrogen 12563)Desferoxiamine (Sigma D9533-1G)One-Glo (Promega E6120)I. Cell Addition1- Dispense 3 uL/well of cells at 2.5x10^5 cells/ml to col 1-48. 2- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.3 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.II. Reagent Addition4-Dispense 1 ul/well 200 uM desferoxiamine in assay media to columns 5-48III. Compound Addition:5- Transfer test compounds to columns 5-44 and DMSO to columns 1-4 and 45-48 using the Labcyte ECHO 555. Transfer volume of test compound is 40-2.5 nl of 10 mM stock and 40-2.5 nl of 0.3125 mM stock. All wells are backfilled to 40nl DMSO (1% DMSO) 6- Spin down plates on Eppendorf centrifuge 5810 at 500 rpm for 1 minute.7 - Put Kalypsis metal lids on plates, incubate plates at 37 oC with 5% C02 overnight.IV. Reagent Addition8- Dispense 3 uL/well of One-Glo using Combi dispenser to all columns.9- Spin down plates without lids on Vspin at 2000 rpm for 1 min10- Incubate plates at room temperature for 10 minsV. Reading plates:11-Read on luminescence protocol on EnvisionCompounds that are active in the IC50_HIF-2a and IC50_HIF-2a_PANC assays and inactive in the IC50_HIF-1a assay are specific inhibitors of the reaction.Compounds that have an IC50_HIF-2a_Mean <= 10 uM are inhibitors of the reaction.Compounds that have IC50_HIF-2a_Mean_PANC < = 10 are inhibitors of the reaction Compounds that have IC50_HIF-1a_Mean <= 10 are non-specific inhibitors of the reaction and marked as inactive and given a score of 81.To simplify the distinction between the inactives of the primary screen and of the confirmatory screening stage, the Tiered Activity Scoring System was developed and implemented. Activity ScoringActivity scoring rules were devised to take into consideration compound efficacy, its potential interference with the assay and the screening stage that the data was obtained. Details of the Scoring System will be published elsewhere. Briefly, the outline of the scoring system utilized for the assay is as follows:1) First tier (0-40 range) is reserved for primary screening data and is not applicable in this assay2) Second tier (41-80 range) is reserved for dose-response confirmation data and is not applicable in this assay3) Third tier (81-100 range) is reserved for resynthesized true positives and their analoguesa. Inactive compounds of the confirmatory stage are assigned a score value equal 81. b. The score is linearly correlated with a compound potency and, in addition, provides a measure of the likelihood that the compound is not an artifact based on the available information.c. The Hill coefficient is taken as a measure of compound behavior in the assay via an additional scaling factor QC: QC = 2.6*[exp(-0.5*nH^2) - exp(-1.5*nH^2)]This empirical factor prorates the likelihood of target-specific compound effect vs. its non-specific behavior in the assay. This factor is based on expectation that a compound with a single mode of action that achieved equilibrium in this assay demonstrates the Hill coefficient value of 1. Compounds deviating from that behavior are penalized proportionally to the degree of their deviation.d. Summary equation that takes into account the items discussed above is Score = 82 + 3*(pIC50 - 3)*QC, where pIC50 is a negative log(10) of the IC50 value expressed in mole/L concentration units. This equation results in the Score values above 85 for compounds that demonstrate high potency and predictable behavior. Compounds that are inactive in the assay or whose concentration-dependent behavior are likely to be an artifact of that assay will generally have lower Score values.6243526243579606homo sapianshttp://cpccg.sanfordburnham.org2034EPAS1 endothelial PAS domain protein 1 [ Homo sapiens ]222776912236791322068265220932551PUBCHEM_ACTIVITY_SCORE_HIF2a2254112PubChem_Activity_Outcome_HIF2a2254123PUBCHEM_ACTIVITY_SCORE_HIF2a_PANC2254414PubChem_Activity_Outcome_HIF2a_Panc2254425PUBCHEM_ACTIVITY_SCORE_HIF1a2254716PubChem_Activity_Outcome_HIF1a2254727IC50_Mean_Qualifier_HIF2aThis qualifier is to be used with the next TID, IC50_Mean. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value4254118IC50_Mean_HIF2aIC50 value determined using a sigmoidal dose response equation15119IC50_Mean_Qualifier_HIF2a (PANC cells)This qualifier is to be used with the next TID, IC50_Mean. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42544110IC50_Mean_HIF2a (PANC cells)IC50 value determined using a sigmoidal dose response equation154111IC50_Mean_Qualifier_HIF1aThis qualifier is to be used with the next TID, IC50_Mean. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42547112IC50_Mean_HIF1aIC50 value determined using a sigmoidal dose response equation157113IC50_Qualifier_1_HIF2aThis qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42542114IC50_1_HIF2aIC50 value determined using a sigmoidal dose response equation152115Std.Err(IC50)_1_HIF2aStandard Error of the IC50 value152116nH_1_HIF2aHill coefficient determined using sigmoidal dose response equation12542117Excluded_Points_first_point_HIF2aFlags to indicate which of the first dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.42542118% Activity at 99 uM_first_point_HIF2a% Activity at the test concentration11599512119% Activity at 49.5 uM_first_point_HIF2a% Activity at the test concentration11549.5512120% Activity at 24.75 uM_first_point_HIF2a% Activity at the test concentration11524.75512121% Activity at 12.375 uM_first_point_HIF2a% Activity at the test concentration11512.375512122% Activity at 6.1875 uM_first_point_HIF2a% Activity at the test concentration1156.1875512123% Activity at 3.09375 uM_first_point_HIF2a% Activity at the test concentration1153.09375512124% Activity at 1.546875 uM_first_point_HIF2a% Activity at the test concentration1151.54688000679016512125% Activity at 0.7734375 uM_first_point_HIF2a% Activity at the test concentration1150.773437976837158512126% Activity at 0.3867188 uM_first_point_HIF2a% Activity at the test concentration1150.386718988418579512127% Activity at 0.1933594 uM_first_point_HIF2a% Activity at the test concentration1150.19335900247097512128IC50_Qualifier_2_HIF2aThis qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42543129IC50_2_HIF2aIC50 value determined using a sigmoidal dose response equation153130Std.Err(IC50)_2_HIF2aStandard Error of the IC50 value153131nH_2_HIF2aHill coefficient determined using sigmoidal dose response equation12543132Excluded_Points_second_point_HIF2aFlags to indicate which of the second dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.42543133% Activity at 99 uM_second_point_HIF2a% Activity at the test concentration11599523134% Activity at 49.5 uM_second_point_HIF2a% Activity at the test concentration11549.5523135% Activity at 24.75 uM_second_point_HIF2a% Activity at the test concentration11524.75523136% Activity at 12.375 uM_second_point_HIF2a% Activity at the test concentration11512.375523137% Activity at 6.1875 uM_second_point_HIF2a% Activity at the test concentration1156.1875523138% Activity at 3.09375 uM_second_point_HIF2a% Activity at the test concentration1153.09375523139% Activity at 1.546875 uM_second_point_HIF2a% Activity at the test concentration1151.54688000679016523140% Activity at 0.7734375 uM_second_point_HIF2a% Activity at the test concentration1150.773437976837158523141% Activity at 0.3867188 uM_second_point_HIF2a% Activity at the test concentration1150.386718988418579523142% Activity at 0.1933594 uM_second_point_HIF2a% Activity at the test concentration1150.19335900247097523143IC50_Qualifier_1_HIF2a_PANCThis qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42545144IC50_1_HIF2a_PANCIC50 value determined using a sigmoidal dose response equation155145Std.Err(IC50)_1_HIF2a_PANCStandard Error of the IC50 value155146nH_1_HIF2a_PANCHill coefficient determined using sigmoidal dose response equation12545147Excluded_Points_first_point_HIF2a_PANCFlags to indicate which of the first dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.42545148% Activity at 99 uM_first_point_HIF2a_PANC% Activity at the test concentration11599535149% Activity at 49.5 uM_first_point_HIF2a_PANC% Activity at the test concentration11549.5535150% Activity at 24.75 uM_first_point_HIF2a_PANC% Activity at the test concentration11524.75535151% Activity at 12.375 uM_first_point_HIF2a_PANC% Activity at the test concentration11512.375535152% Activity at 6.1875 uM_first_point_HIF2a_PANC% Activity at the test concentration1156.1875535153% Activity at 3.09375 uM_first_point_HIF2a_PANC% Activity at the test concentration1153.09375535154% Activity at 1.546875 uM_first_point_HIF2a_PANC% Activity at the test concentration1151.54688000679016535155% Activity at 0.7734375 uM_first_point_HIF2a_PANC% Activity at the test concentration1150.773437976837158535156% Activity at 0.3867188 uM_first_point_HIF2a_PANC% Activity at the test concentration1150.386718988418579535157% Activity at 0.1933594 uM_first_point_HIF2a_PANC% Activity at the test concentration1150.19335900247097535158IC50_Qualifier_2_HIF2a_PANCThis qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42546159IC50_2_HIF2a_PANCIC50 value determined using a sigmoidal dose response equation156160Std.Err(IC50)_2_HIF2a_PANCStandard Error of the IC50 value156161nH_2_HIF2a_PANCHill coefficient determined using sigmoidal dose response equation12546162Excluded_Points_second_point_HIF2a_PANCFlags to indicate which of the second dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.42546163% Activity at 99 uM_second_point_HIF2a_PANC% Activity at the test concentration11599546164% Activity at 49.5 uM_second_point_HIF2a_PANC% Activity at the test concentration11549.5546165% Activity at 24.75 uM_second_point_HIF2a_PANC% Activity at the test concentration11524.75546166% Activity at 12.375 uM_second_point_HIF2a_PANC% Activity at the test concentration11512.375546167% Activity at 6.1875 uM_second_point_HIF2a_PANC% Activity at the test concentration1156.1875546168% Activity at 3.09375 uM_second_point_HIF2a_PANC% Activity at the test concentration1153.09375546169% Activity at 1.546875 uM_second_point_HIF2a_PANC% Activity at the test concentration1151.54688000679016546170% Activity at 0.7734375 uM_second_point_HIF2a_PANC% Activity at the test concentration1150.773437976837158546171% Activity at 0.3867188 uM_second_point_HIF2a_PANC% Activity at the test concentration1150.386718988418579546172% Activity at 0.1933594 uM_second_point_HIF2a_PANC% Activity at the test concentration1150.19335900247097546173IC50_Qualifier_1_HIF1aThis qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42548174IC50_1_HIF1aIC50 value determined using a sigmoidal dose response equation158175Std.Err(IC50)_1_HIF1aStandard Error of the IC50 value158176nH_1_HIF1aHill coefficient determined using sigmoidal dose response equation12548177Excluded_Points_first_point_HIF1aFlags to indicate which of the first dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.42548178% Activity at 99 uM_first_point_HIF1a% Activity at the test concentration11599558179% Activity at 49.5 uM_first_point_HIF1a% Activity at the test concentration11549.5558180% Activity at 24.75 uM_first_point_HIF1a% Activity at the test concentration11524.75558181% Activity at 12.375 uM_first_point_HIF1a% Activity at the test concentration11512.375558182% Activity at 6.1875 uM_first_point_HIF1a% Activity at the test concentration1156.1875558183% Activity at 3.09375 uM_first_point_HIF1a% Activity at the test concentration1153.09375558184% Activity at 1.546875 uM_first_point_HIF1a% Activity at the test concentration1151.54688000679016558185% Activity at 0.7734375 uM_first_point_HIF1a% Activity at the test concentration1150.773437976837158558186% Activity at 0.3867188 uM_first_point_HIF1a% Activity at the test concentration1150.386718988418579558187% Activity at 0.1933594 uM_first_point_HIF1a% Activity at the test concentration1150.19335900247097558188IC50_Qualifier_2_HIF1aThis qualifier is to be used with the next TID, . If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value42549189IC50_2_HIF1aIC50 value determined using a sigmoidal dose response equation159190Std.Err(IC50)_2_HIF1aStandard Error of the IC50 value159191nH_2_HIF1aHill coefficient determined using sigmoidal dose response equation12549192Excluded_Points_second_point_HIF1aFlags to indicate which of the second dose-response points were excluded from analysis. (1) means the titration point was excluded and (0) means the point was not excluded.42549193% Activity at 99 uM_second_point_HIF1a% Activity at the test concentration11599569194% Activity at 49.5 uM_second_point_HIF1a% Activity at the test concentration11549.5569195% Activity at 24.75 uM_second_point_HIF1a% Activity at the test concentration11524.75569196% Activity at 12.375 uM_second_point_HIF1a% Activity at the test concentration11512.375569197% Activity at 6.1875 uM_second_point_HIF1a% Activity at the test concentration1156.1875569198% Activity at 3.09375 uM_second_point_HIF1a% Activity at the test concentration1153.09375569199% Activity at 1.546875 uM_second_point_HIF1a% Activity at the test concentration1151.546880006790165691100% Activity at 0.7734375 uM_second_point_HIF1a% Activity at the test concentration1150.7734379768371585691101% Activity at 0.3867188 uM_second_point_HIF1a% Activity at the test concentration1150.3867189884185795691102% Activity at 0.1933594 uM_second_point_HIF1a% Activity at the test concentration1150.1933590024709756911endothelial PAS domain-containing protein 1 [Homo sapiens]402544391Homo sapienshumantaxon960621CR Plot Labels 1ConcentrationResponse02CR Plot Labels 2ConcentrationResponse03CR Plot Labels 3ConcentrationResponse04CR Plot Labels 4ConcentrationResponse05CR Plot Labels 5ConcentrationResponse06CR Plot Labels 6ConcentrationResponse01 R03 DA033980-01A12HIF-2a panel1IC50_Mean_HIF2aIC50_Mean value determined using a sigmoidal dose response equation for the replicatesendothelial PAS domain-containing protein 1 [Homo sapiens]4025443912IC50_1_HIF2aIC50 value determined using a sigmoidal dose response equationendothelial PAS domain-containing protein 1 [Homo sapiens]4025443913IC50_2_HIF2aIC50 value determined using a sigmoidal dose response equationendothelial PAS domain-containing protein 1 [Homo sapiens]4025443914IC50_Mean_Qualifier_HIF2a (PANC cells)IC50_Mean value determined using a sigmoidal dose response equation for the replicatesendothelial PAS domain-containing protein 1 [Homo sapiens]4025443915IC50_1_HIF2a_PANCIC50 value determined using a sigmoidal dose response equationendothelial PAS domain-containing protein 1 [Homo sapiens]4025443916IC50_2_HIF2a_PANCIC50 value determined using a sigmoidal dose response equationendothelial PAS domain-containing protein 1 [Homo sapiens]4025443917IC50_Mean_HIF1aIC50_Mean value determined using a sigmoidal dose response equation for the replicateshypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens]450438518IC50_1_HIF1aIC50 value determined using a sigmoidal dose response equationhypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens]450438519IC50_2_HIF1aIC50 value determined using a sigmoidal dose response equationhypoxia-inducible factor 1-alpha isoform 1 [Homo sapiens]45043851